Endothelial Gata5 transcription factor regulates blood pressure

Smail Messaoudi; Ying He; Alex Gutsol; Andrew Wight; Richard L. Hébert; Ragnar O. Vilmundarson; Andrew P. Makrigiannis; John Chalmers; Pavel Hamet; Johanne Tremblay; Ruth McPherson; Alexandre F.R. Stewart; Rhian M. Touyz; Mona Nemer

doi:10.1038/ncomms9835

Endothelial Gata5 transcription factor regulates blood pressure

Smail Messaoudi, Ying He, Alex Gutsol, Andrew Wight, Richard L. Hébert, Ragnar O. Vilmundarson, Andrew P. Makrigiannis, John Chalmers, Pavel Hamet, Johanne Tremblay, Ruth McPherson, Alexandre F.R. Stewart, Rhian M. Touyz, Mona Nemer

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Despite its high prevalence and economic burden, the aetiology of human hypertension remains incompletely understood. Here we identify the transcription factor GATA5, as a new regulator of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells and its genetic inactivation in mice (Gata5-null) leads to vascular endothelial dysfunction and hypertension. Endothelial-specific inactivation of Gata5 mimics the hypertensive phenotype of the Gata5-null mice, suggestive of an important role for GATA5 in endothelial homeostasis. Transcriptomic analysis of human microvascular endothelial cells with GATA5 knockdown reveals that GATA5 affects several genes and pathways critical for proper endothelial function, such as PKA and nitric oxide pathways. Consistent with a role in human hypertension, we report genetic association of variants at the GATA5 locus with hypertension traits in two large independent cohorts. Our results unveil an unsuspected link between GATA5 and a prominent human condition, and provide a new animal model for hypertension.

Original language	English
Article number	8835
Number of pages	13
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9835
Publication status	Published - 30 Nov 2015
Externally published	Yes

Bibliographical note

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Keywords

Hypertension
Transcriptomics
Medical research
Transcription factors

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Messaoudi, Smail ; He, Ying ; Gutsol, Alex ; Wight, Andrew ; Hébert, Richard L. ; Vilmundarson, Ragnar O. ; Makrigiannis, Andrew P. ; Chalmers, John ; Hamet, Pavel ; Tremblay, Johanne ; McPherson, Ruth ; Stewart, Alexandre F.R. ; Touyz, Rhian M. ; Nemer, Mona. / Endothelial Gata5 transcription factor regulates blood pressure. In: Nature Communications. 2015 ; Vol. 6.

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Endothelial Gata5 transcription factor regulates blood pressure. / Messaoudi, Smail; He, Ying; Gutsol, Alex; Wight, Andrew; Hébert, Richard L.; Vilmundarson, Ragnar O.; Makrigiannis, Andrew P.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; McPherson, Ruth; Stewart, Alexandre F.R.; Touyz, Rhian M.; Nemer, Mona.

In: Nature Communications, Vol. 6, 8835, 30.11.2015.

Research output: Contribution to journal › Article › peer-review

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AU - Tremblay, Johanne

AU - McPherson, Ruth

AU - Stewart, Alexandre F.R.

AU - Touyz, Rhian M.

AU - Nemer, Mona

N1 - This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

PY - 2015/11/30

Y1 - 2015/11/30

N2 - Despite its high prevalence and economic burden, the aetiology of human hypertension remains incompletely understood. Here we identify the transcription factor GATA5, as a new regulator of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells and its genetic inactivation in mice (Gata5-null) leads to vascular endothelial dysfunction and hypertension. Endothelial-specific inactivation of Gata5 mimics the hypertensive phenotype of the Gata5-null mice, suggestive of an important role for GATA5 in endothelial homeostasis. Transcriptomic analysis of human microvascular endothelial cells with GATA5 knockdown reveals that GATA5 affects several genes and pathways critical for proper endothelial function, such as PKA and nitric oxide pathways. Consistent with a role in human hypertension, we report genetic association of variants at the GATA5 locus with hypertension traits in two large independent cohorts. Our results unveil an unsuspected link between GATA5 and a prominent human condition, and provide a new animal model for hypertension.

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Endothelial Gata5 transcription factor regulates blood pressure

Abstract

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